4-Pyridinemethanamine → Racemic-(trans)-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}-n-(4-pyridinylmethyl)cyclopropanecarboxamide

HRID 1173022

Reaction equation

HRID 1173022 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]1[N:27]=[C:28]([C:45]2[CH:50]=[CH:49][C:48]([C:51]([F:54])([F:53])[F:52])=[CH:47][CH:46]=2)[S:29][C:30]=1[CH2:31][NH:32][C:33]1[CH:38]=[CH:37][C:36]([C@@H:39]2[CH2:41][C@H:40]2[C:42](O)=[O:43])=[CH:35][CH:34]=1.[N:55]1[CH:60]=[CH:59][C:58]([CH2:61][NH2:62])=[CH:57][CH:56]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.C(OCC)(=O)C>[CH3:25][C:26]1[N:27]=[C:28]([C:45]2[CH:46]=[CH:47][C:48]([C:51]([F:54])([F:52])[F:53])=[CH:49][CH:50]=2)[S:29][C:30]=1[CH2:31][NH:32][C:33]1[CH:34]=[CH:35][C:36]([C@@H:39]2[CH2:41][C@H:40]2[C:42]([NH:62][CH2:61][C:58]2[CH:59]=[CH:60][N:55]=[CH:56][CH:57]=2)=[O:43])=[CH:37][CH:38]=1

Participants

7

Reactant 4

HCID 773174-PyridinemethanamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11487291(+)-(trans)-2-{4-[({4-Methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}cyclopropanecarboxylic acid

Product 1

HCID 11352951Racemic-(trans)-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}-n-(4-pyridinylmethyl)cyclopropanecarboxamideYield 64.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (0.14 g, 0.37 mmol) and racemic-(trans)-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}cyclopropanecarboxylic acid (I-2m) (0.12 g, 0.28 mmol) in DMF (10 mL) were stirred at RT for 45 min, then (4-pyridinylmethyl)amine (0.36 g, 3.33 mmol) was added. The solution was stirred at RT for 16 h, then saturated NaHCO3 solution (50 mL) and ethyl acetate (50 mL) were added. The organic layer was separated, washed with saturated NaHCO3 solution (50 mL), water (50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated. The crude material was partially dissolved in dichloromethane (10 mL) and diethyl ether was added (10 mL). The white solid was filtered, washed with diethyl ether, and dried to give the title compound as a white powder (0.094 g, 64%). 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J=5.1 Hz, 2H), 7.97 (d, J=8.4 Hz, 2H), 7.65 (d, J=8.2 Hz, 2H), 7.20 (d, J=4.7 Hz, 2H), 6.96 (d, J=8.1 Hz, 2H), 6.60 (d, J=8.4 Hz, 2H), 5.99 (t, J=5.7 Hz, 1H), 4.49 (t, J=5.9 Hz, 2H), 4.45 (s, 2H), 4.02 (bs, 1H), 2.49 (s, 3H), 2.49-2.45 (m, 1H), 1.63-1.53 (m, 2H), 1.25-1.21 (m, 1H). ES-MS m/z 523.2 (MH+).

Workup

  1. customThe organic layer was separated
  2. washwashed with saturated NaHCO3 solution (50 mL), water (50 mL), brine (50 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude material was partially dissolved in dichloromethane (10 mL)
  7. additiondiethyl ether was added (10 mL)
  8. filtrationThe white solid was filtered
  9. washwashed with diethyl ether
  10. customdried

Sources & evidence

ORD record
ord-4fc12eb51bbe48c8888107d2c2ecfcb4
Source dataset
uspto-grants-2010_11
Patent number
US07834013B2

Linked notes

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